The S100 calcium binding protein B gene (S1008) encodes the S100B Protein which is expressed and secreted by glial cells and astrocytes of the brain (Vives et al. 2003). The overexpression of the S100B protein has been associated with the neurodegeneration in Alzheimer's Disease (Leclerc E et al. 2010) and Parkinson Disease (Sathe K et al. 2012). Furthermore, serum level alterations of the S100B protein have been reported as a potential biomarker for a variety of disease indications including arterial hypertension (Gruden M A et al. 2014), preeclampsia (Bergman et al. 2014) and traumautic brain injury (Yokobori S et al. 2013).
There is a need for characterized human S100B promoters for gene expression, for instance in human gene therapy applications. It is particularly useful to identify small promoter elements that are sufficient to drive expression in regions of the brain, for instance in the glial cells or astrocytes in the central nervous system as well as in Müller glia in the retina. Such small promoter elements, or “mini-promoters” are particularly useful in certain applications, for instance they are more amenable to insertion into viral vectors used in gene therapy applications.
S100B promoter elements described in the art, including:
Dagdan E, Morris D W, Campbell M, Hill M, Rothermundt M, Kästner F, Hohoff C, von Eiff C, Krakowitzky P, Gill M, McKeon P, Roche S. Functional assessment of a promoter polymorphism in S100B, a putative risk variant for bipolar disorder. Am J Med Genet B Neuropsychiatr Genet. 2011 September; 156B(6):691-9.
Pustylnyak V O, Lisachev P D, Shtark M B, Epstein O I. Regulation of S100B gene in rat hippocampal CA1 area during long term potentiation. Brain Res. 2011 Jun. 7; 1394:33-9.
Geller S F, Ge P S, Visel M, Flannery J G. In vitro analysis of promoter activity in Müller cells. Mol Vis. 2008 Apr. 23; 14:691-705.
US2009-0280568 A1 describes earlier S100B mini-promoters designs by the inventors.